Trisomy 21 (i.e., one additional 21st chromosome) accounts for 95 per cent of all cases of Down syndrome. This condition is among the most common genetic defects, occurring in about 1 in every 800 births. Patients with this syndrome have characteristic faces, are mentally retarded, and at least 30 per cent have congenital heart disease.
Trisomy 21 occurs when homologous chromosomes fail to separate at anaphase, resulting in nondisjunction and the production of one monosomic and one trisomic daughter nuclei. In chromosomally normal women, the frequency of nondisjunction is age related. For women ages 20 to 30, the incidence increases linearly from about 0.3 per 1000 births to about 2 per 1000 births. After the age of 30, the incidence increases exponentially, at a rate of about 30 per cent per year. Women over 35 give birth to 35 per cent of all children with Trisomy 21 Down Syndrome.
Women under 20 also show an increasing incidence of Trisomy 21 Down syndrome with falling age. Thus, a woman age 15 has about the same chance of having a Down syndrome child as a woman between the ages of 30 and 35.
The risk for a woman under the age of 30 of having a second child with Trisomy 21 Down syndrome is 1.4 per cent. Her risk after the age of 30 is 1 per cent plus the risk factor for a woman of that age.
The nondisjunction which results in Trisomy 21 Down syndrome can also occur in the male. Nondisjunction in the male accounts for 20 to 25% of children with this syndrome. For fathers over the age of 55, the risk of having a Down syndrome child may be about twice that expected after adjustment for the mother's age.
Prior to birth, a fetus with genetic defects (including Trisomy 21) can be detected through amniocentesis. In amniocentesis 10 to 20 ml of amniotic fluid are withdrawn from the amniotic cavity between the 15th and 16th week of pregnancy. The amniotic fluid cells are then cultured in tissue culture for about two weeks. The cells are stained, and the chromosomes are counted to identify genetic abnormalities such as Trisomy 21.
Cell culturing is, however, an expensive, skilled laborintensive, and time-consuming process, often costing up to $1200. Further, the cultures are easily destroyed if contamination enters. Thus, prior to cell culturing, the fluid is often screened for proteins which indicate the existence of certain defects (so-called "genetic markers.") If the screening is positive, cell culturing can then be done to verify the existence of the defect. If negative, the expense of culturing can be foregone. Screening is currently commonplace, because many pregnant women are now being advised to have amniotic fluid withdrawn and screened for the genetic marker Alpha Fetoprotein ("AFP").
Elevated levels of AFP indicate open neural tube defects, such as anencephaly and Spina Bifida, as well as other fetal abnormalities. Although some women carrying a Trisomy 21 fetus will show abnormal AFP levels, many will show no deviation from normal limits.
Thus, the current screening tests for Trisomy 21 are deficient. Further, because of the expense of the more accurate cell culturing technique, this test is often foregone by the patient. In view of the frequency with which Trisomy 21 occurs, a marker (and a screening test based on such marker) which gave a truer indication of the presence of Trisomy 21 would clearly be desirable, particularly for women in the higher risk groups.
By 1981 it was recognized that Trisomy 21 patients showed increased levels of SOD-1 in Red Blood Cell lysates. See B. C. Del Villano & J. A. Tischfield, "Quantitation of Human Cuprozinc SOD-1 by Radioimmunoassay and Its Possible Significance in Disease," Immunoassay Methods at 366-67 (1981). However, there is no suggestion in this article to screen body fluid for SOD-1 as a test for Trisomy 21. The authors only state that this discovery could shed light on the role of SOD-1 in normal metabolism, or indicate the consequences of having excess SOD-1. They also indicate that further experiments could relate the SOD-1 level to the degree of retardation.
A 1985 study sought to determine whether increased levels of SOD-1 were to be found in Trisomy 21 fetal fibroblasts, amniotic cells and amniotic fluid. See M. A. Bateman, M. G. Mattei, A. Abret, M. Gamerre & J. F. Mattei, "Immunoreactive SOD-1 in Amniotic Fluid, Amniotic Cells and Fibroblasts from Trisomy 21 Fetus," Acta Poediatr. Scand. 74:697-700 (1985). The authors concluded that it was not possible to establish a relationship between SOD-1 levels in amniotic fluid and Trisomy 21 in the fetus. Id. at 699. Thus, if increased SOD-1 levels in amniotic fluid (or other body fluids of the mother) correlated with a Trisomy 21 fetus, this would be a significant departure from the teachings of the prior art.